Yonsei Med J.  2006 Oct;47(5):604-613. 10.3349/ymj.2006.47.5.604.

High Dose Chemotherapy and Autologous Stem Cell Transplantation in Non-Hodgkin's Lymphoma: an Eight-Year Experience

• Chang H
• Cheong JW
• Hahn JS

• KMID: 1381241
• DOI: http://doi.org/10.3349/ymj.2006.47.5.604

Abstract

Autologous stem cell transplantation (ASCT) is commonly used in relapsed or refractory non-Hodgkin's lymphoma (NHL). Several trials report the role of ASCT for high risk patients. We evaluated the results and the prognostic factors influencing the therapeutic effects on the patients who were treated with high dose chemotherapy (HDC) and autologous peripheral stem cell transplantation. We analyzed the data of 40 cases with NHL who underwent ASCT after HDC. Twenty- four patients had high-risk disease, 12 cases sensitive relapse, and two cases resistant relapse or primary refractory each. The median age of patients was 34 years (range, 14-58 years). The median follow-up duration from transplantation was 16 months (range, 0.6-94 months). Estimated overall survival and progression-free survival at 5 years were 40% and 30%, respectively. Poor prognostic factors for survival included older age (> or = 45 years), poor performance status in all patient analysis, and a longer interval between first complete remission and transplantation in high risk patients. In high risk NHL patients, transplantation should be done early after first complete remission to overcome chemo-resistance.

Keyword

Transplantation; autologous; stem cells; lymphoma; non-Hodgkin

MeSH Terms

Transplantation, Autologous
Survival Rate
Risk Factors
Retrospective Studies
Prognosis
Platelet Count
*Peripheral Blood Stem Cell Transplantation
Middle Aged
Male
Lymphoma, Non-Hodgkin/diagnosis/drug therapy/*therapy
Leukocyte Count
Humans
Female
Combined Modality Therapy
Adult
Adolescent

Figure

• 

  Fig. 1 Overall survival (-) and progression free survival (---) rates of all patients.

• 

  Fig. 2 (A) Overall survival rates according to disease status at transplantation. High risk vs. Resistant relapse, p = 0.37; Sensitive relapse vs. Resistant relapse, p = 0.68. (B) Progression free survival rates according to disease status at transplantation. High risk vs. Resistant relapse, p = 0.59; Sensitive relapse vs. Resistant relapse, p = 0.85.

• 

  Fig. 3 Overall survival rates according to interval from CR to transplantation in high risk patients.

Reference

1. Elias L, Portlock CS, Rosenberg SA. Combination chemotherapy of diffuse histiocytic lymphoma with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP). Cancer. 1978; 42:1705–1710. PMID: 361209.

2. Coiffier B. State-of-the-art therapeutics: diffuse large B-cell lymphoma. J Clin Oncol. 2005; 23:6387–6393. PMID: 16155024.

3. Armitage JO. Treatment of non-Hodgkin's lymphoma. N Engl J Med. 1993; 328:1023–1030. PMID: 8450856.

4. Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, et al. Comparision of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993; 328:1002–1006. PMID: 7680764.

5. Mills W, Chopra R, McMillan A, Pearce R, Linch DC, Goldstone AH. BEAM chemotherapy and autologous bone marrow transplantation for patients with relapsed or refractory non-Hodgkin's lymphoma. J Clin Oncol. 1995; 13:588–595. PMID: 7884420.

6. Philip T, Armitage JO, Spitzer G, Chauvin F, Jagannath S, Cahn JY, et al. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. N Engl J Med. 1987; 316:1493–1498. PMID: 3295541.

7. Verdonck LF, Dekker AW, van Kempen ML, Punt K, van Unnik JA, van Peperzeel HA, et al. Intensive cytotoxic therapy followed by autologous bone marrow transplantation for non-Hodgkin's lymphoma of high-grade malignancy. Blood. 1985; 65:984–989. PMID: 3884064.

8. Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995; 333:1540–1545. PMID: 7477169.

9. Haioun C, Lepage E, Gisselbrecht C, Salles G, Coiffier B, Brice P, et al. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2 protocol-a groupe d'Etude des lymphomes de l'Adulte study. J Clin Oncol. 2000; 18:3025–3030. PMID: 10944137.

10. Santini G, Salvagno L, Leoni P, Chisesi T, De Souza C, Sertoli MR, et al. VACOP-B versus VACOP-B plus autologous bone marrow transplantation for advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the Non-Hodgkin's Lymphoma Cooperative Study Group. J Clin Oncol. 1998; 16:2796–2802. PMID: 9704732.

11. Kaiser U, Uebelacker I, Abel U, Birkmann J, Trumper L, Schmalenberg H, et al. Randomized study to evaluate the use of high-dose therapy as part of primary treatment for aggressive lymphoma. J Clin Oncol. 2002; 20:4413–4419. PMID: 12431962.

12. Krauter J, Gorlich K, Ottmann O, Lubbert M, Dohner H, Heit W, et al. Early autologous stem-cell transplantation versus conventional chemotherapy as front-line therapy in high-risk, aggressive non-Hodgkin's lymphoma: an Italian multicenter randomized trial. J Clin Oncol. 2003; 21:1255–1262. PMID: 12663712.

13. Gisselbrecht C, Lepage E, Molina T, Quesnel B, Fillet G, Lederlin P, et al. Shortened first-line high-dose chemotherapy for patients with poor-prognosis aggressive lymphoma. J Clin Oncol. 2002; 20:2472–2479. PMID: 12011124.

14. Hennessy BT, Hanrahan EO, Daly PA. Non-Hodgkin lymphoma: an update. Lancet Oncol. 2004; 5:341–353. PMID: 15172354.

15. Bertz H, Zeiser R, Lange W, Fetscher S, Waller CF, Finke J. Long-term follow-up after high-dose chemotherapy and autologous stem-cell transplantation for high-grade B-cell lymphoma suggests an improved outcome for high-risk patients with respect to the age-adjusted International Prognostic Index. Ann Oncol. 2004; 15:1419–1424. PMID: 15319249.

16. Harry C. High dose Therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial. J Clin Oncol. 2003; 21:3918–3927. PMID: 14517188.

17. Laudi N, Arora M, Burns LJ, Miller JS, McGlave PB, Barker JN, et al. Long-term follow-up after autologous hematopoietic stem cell transplantation for low-grade non-Hodgkin lymphoma. Biol Blood Marrow Transplant. 2005; 11:129–135. PMID: 15682074.

18. National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: summary and description of a working formulation for clinical usage. The Non-Hodgkin's Lymphoma Pathologic Classification Project. Cancer. 1982; 49:2112–2135. PMID: 6896167.

19. Shipp MA, Abeloff MD, Antman KH, Carroll G, Hagenbeek A, Loeffler M, et al. International Consensus Conference on High-Dose Therapy with Hematopoietic Stem Cell Transplantation in Aggressive Non-Hodgkin's Lymphomas: report of the jury. J Clin Oncol. 1999; 17:423–429. PMID: 10458261.

20. Schmitz N, Linch DC, Dreger P, Goldstone AH, Boogaerts MA, Ferrant A, et al. Randomised trial of filgrastin-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients. Lancet. 1996; 347:353–357. PMID: 8598700.

21. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999; 17:1244–1253. PMID: 10561185.

22. A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med. 1993; 329:987–994. PMID: 8141877.

23. Caballero MD, Perez-Simon JA, Iriondo A, Lahuerta JJ, Sierra J, Marin J, et al. High-dose therapy in diffuse large cell lymphoma: results and prognostic factors in 452 patients from the GEL-TAMO Spanish Cooperative Group. Ann Oncol. 2003; 14:140–151. PMID: 12488306.

24. Kim YK, Lee JJ, Ahn JS, Yang DH, Byun JR, Cho SH, et al. High-dose therapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma; a single center experience. Korean J Hematol Stem Cell Trans. 2004; 9:12–18.

25. Shim BY, Lee MA, Byun JH, Roh SY, Song CW, Park JN, et al. High dose chemotherapy and autologous stem cell transplantation for poor risk and recurrent non-Hodgkin's lymphoma: a single-center experience of 50 patients. Korean J Intern Med. 2004; 19:114–120. PMID: 15366643.

26. Dowling AJ, Prince HM, Wirth A, Wolf M, Januszewicz EH, Juneja S, et al. High-dose therapy and autologous transplantation for lymphoma: The Peter MacCallum Cancer Institute experience. Intern Med J. 2001; 31:279–289. PMID: 11512599.

27. Rodriguez J, Caballero MD, Gutierrez A, Marin J, Lahuerta JJ, Sureda A, et al. High-dose chemotherapy and autologous stem cell transplantation in peripheral T-cell lymphoma: the GEL-TAMO experience. Ann Oncol. 2003; 14:1768–1775. PMID: 14630683.

28. Gisselbrecht C, Gaulard P, Lepage E, Coiffier B, Briere J, Haioun C, et al. Prognostic significance of T-cell phenotype in aggressive non-Hodgkin's lymphomas. Groupe d'Etudes des Lymphomes de l'Adulte (GELA). Blood. 1998; 92:76–82. PMID: 9639502.

29. The world health organization classification of malignant lymphomas in Japan: incidence of recently recognized entities. Lymphoma Study Group of Japanese Pathologists. Pathol Int. 2000; 50:696–702. PMID: 11012982.

30. Hahn JS, Lee S, Chong SY, Min YH, Ko YW. Eight-year experience of malignant lymphoma; survival and prognostic factors. Yonsei Med J. 1997; 38:270–284. PMID: 9409190.

31. Ko YH, Kim CW, Park CS, Jang HK, Lee SS, Kim SH, et al. REAL classification of malignant lymphomas in the Republic of Korea: incidence of recently recognized entities and changes in clinicopathologic features. Hematolymphoreticular Study Group of the Korean Society of Pathologists. Revised European-American lymphoma. Cancer. 1998; 83:806–812. PMID: 9708949.

32. Cuttica A, Zallio F, Ladetto M, Di Nicola M, Caracciolo D, Magni M, et al. Patients with high-risk aggressive lymphoma treated with frontline intensive chemotherapy and autografting: evidence of marked differences in outcome between patients with age-adjusted International Prognostic Index scores 2 and 3. Cancer. 2003; 98:983–992. PMID: 12942566.

33. Martelli M, Gherlinzoni F, De Renzo A, Zinzani PL, De Vivo A, Cantonetti M, et al. Early autologous stem-cell transplantation versus conventional chemotherapy as front-line therapy in high-risk, aggressive non-Hodgkin's lymphoma: an Italian multicenter randomized trial. J Clin Oncol. 2003; 21:1255–1262. PMID: 12663712.

34. Milpied N, Deconinck E, Gaillard F, Delwail V, Foussard C, Berthou C, et al. Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support. N Engl J Med. 2004; 350:1287–1295. PMID: 15044639.

35. van Imhoff GW, van der Holt B, Mackenzie MA, Van't Veer MB, Wijermans PW, Ossenkoppele GJ, et al. Impact of three courses of intensified CHOP prior to high-dose sequential therapy followed by autologous stem-cell transplantation as first-line treatment in poor-risk, aggressive non-Hodgkin's lymphoma: comparative analysis of Dutch-Belgian Hemato-Oncology Cooperative Group Studies 27 and 40. J Clin Oncol. 2005; 23:3793–3801. PMID: 15809447.

36. Vose JM, Zhang MJ, Rowlings PA, Lazarus HM, Bolwell BJ, Freytes CO, et al. Autologous transplantation for diffuse aggressive non-Hodgkin's lymphoma in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol. 2001; 19:406–413. PMID: 11208832.

37. Rodriguez J, Caballero MD, Gutierrez A, Solano C, Arranz R, Lahuerta JJ, et al. Autologous stem-cell transplantation in diffuse large B-cell non-Hodgkin's lymphoma not achieving complete response after induction chemotherapy: the GEL/TAMO experience. Ann Oncol. 2004; 15:1504–1509. PMID: 15367411.

38. Mounier N, Gisselbrecht C, Briere J, Haioun C, Feugier P, Offner F, et al. Prognostic factors in patients with aggressive non-Hodgkin's lymphoma treated by front-line autotransplantation after complete remission: a cohort study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2004; 15:2826–2834. PMID: 15254050.

39. Buske C, Dreyling M, Unterhalt M, Hiddemann W. Transplantation strategies for patients with follicular lymphoma. Curr Opin Hematol. 2005; 12:266–272. PMID: 15928482.

40. Cheong JW, Kim JS, Jang JH, Suh HC, Lee ST, Kim HO, et al. Nonmyeloablative stem cell transplantation in a patient with NK/T cell lymphoma. Korean J Hematol Stem Cell Trans. 2001; 6:229–236.

41. Wadhwa P, Shina DC, Schenkein D, Lazarus HM. Should involved-field radiation therapy be used as an adjunct to lymphoma autotransplantation? Bone Marrow Transplant. 2002; 29:183–189. PMID: 11859389.

42. Mundt AJ, Williams SF, Hallahan D. High dose chemotherapy and stem cell rescue for aggressive non-Hodgkin's lymphoma: pattern of failure and implications for involved-field radiotherapy. Int J Radiat Oncol Biol Phys. 1997; 39:617–625. PMID: 9336141.